Harnessing antiviral RNAi therapeutics for pandemic viruses: SARS-CoV-2 and HIV.

Using the knowledge from decades of research into RNA-based therapies, the COVID-19 pandemic response saw the rapid design, testing and production of the first ever mRNA vaccines approved for human use in the clinic. This breakthrough has been a significant milestone for RNA therapeutics and vaccines, driving an exponential growth of research into the field. The development of novel RNA therapeutics targeting high-threat pathogens, that pose a substantial risk to global health, could transform the future of health delivery. In this review, we provide a detailed overview of the two RNA interference (RNAi) pathways and how antiviral RNAi therapies can be used to treat acute or chronic diseases caused by the pandemic viruses SARS-CoV-2 and HIV, respectively. We also provide insights into short-interfering RNA (siRNA) delivery systems, with a focus on how lipid nanoparticles can be functionalized to achieve targeted delivery to specific sites of disease. This review will provide the current developments of SARS-CoV-2 and HIV targeted siRNAs, highlighting strategies to advance the progression of antiviral siRNA along the clinical development pathway.